A Case Report of Tyrosine Kinase Inhibitor Interruption in a Patient with Multilineage Philadelphia-Positive Acute Lymphoblastic Leukemia

INTRODUCTION: Measurable residual disease (MRD) assessment in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) commonly relies on reverse transcription polymerase chain reaction detection of BCR::ABL1 transcripts. However, discordance between BCR::ABL1 PCR and next-generation sequencing (NGS)-based MRD assays targeting immunoglobulin/T-cell receptor (IG/TR) rearrangements may occur, particularly in cases of multilineage Ph+ ALL, complicating treatment decisions such as tyrosine kinase inhibitor (TKI) discontinuation. CASE PRESENTATION: We report a 54-year-old female with Ph+ ALL who achieved durable remission with sustained NGS MRD negativity by IG/TR despite persistent low-level BCR::ABL1 transcript positivity. Following self-discontinuation of ponatinib, she experienced a rapid rise in BCR::ABL1 transcripts and loss of cytogenetic remission in myeloid cells, while remaining morphologically in remission and NGS MRD-negative. Reintroduction of ponatinib resulted in a prompt transcript decline. CONCLUSION: This case highlights the clinical significance of multilineage Ph+ ALL and its distinct biological background, thereby underscoring caution with TKI discontinuation despite deep NGS MRD negativity and may support continued TKI therapy in this setting.